Although people who are homozygous for sickle hemoglobin have a serious disease, sickle cell anemia, people with sickle cell trait who are heterozygous for sickle hemoglobin are healthy and make excellent blood donors. However, blood from patients with sickle cell trait often occludes filters that remove leukocytes from red blood cell components intended for transfusion. Since most hospitals only transfuse red blood cells that have been filtered to remove red blood cells, people with sickle cell trait can no longer donate red blood cells. These studies investigated the causes and prevention of the occlusion of leukocyte reduction filters by blood from patients with sickle cell trait. While at physiological conditions, sickle hemoglobin (hemoglobin S) in red cells from patients with sickle cell trait does not polymerize, at very low oxygen levels, low pH, and high hemoglobin concentrations hemoglobin S in red cells from people with sickle cell trait can polymerize. We have found that hemoglobin S polymerization due to low oxygen tension in venous blood and low pH and high osmolarity of the citrate anticoagulant used for blood collection is responsible for the failure of red blood cell components from donors with sickle cell trait to filter. Red blood cells with polymerized hemoglobin S become stiff and viscous and are unable to pass through leukocyte reduction filters. We found that increasing the oxygen tension in red blood cell components collected from donors with sickle cell trait allowed the red cells be pass through leukocyte reduction filters. When hemoglobin oxygen saturations increased to greater than 60% red blood cell components from donors with sickle cell trait filtered effectively. We tested the effects of bag type and size on the oxygenation of stored red blood cells. We found that standard sized bags made from plastics that were approved for the storage of red cells for transfusion did not transfer enough oxygen to allow sufficient increases in hemoglobin oxygen saturation to allow effective filtration. We are currently investigating the effects of an alternate method of blood collection on hemoglobin S polymerization and the filterability of red cell components from patients with hemoglobin S. Sickle trait red blood cell components collected with a device that automatically added small quantities of citrate anticoagulant to the blood as it was collected allowed the sickle trait blood to pass through the leukocyte reduction filters, but leukocytes were not effectively removed. Future studies will assess the effects of modifying the automated collection device to add less citrate anticoagulant to the collected blood.